DECREASED FRACTIONAL RENAL EXCRETION OF GENTAMICIN IN SUBTOTAL NEPHRECTOMIZED DOGS

Abstract

The effects of subtotal surgical nephrectomy (3/4 removal of renal mass) on the renal handling of gentamicin in the dog were determined. At 3.5 mo. after surgery, dogs were anesthetized and steady-state clearances of gentamicin, creatinine, inulin and p-aminohippurate were determined. Subtotal nephrectomy proportionately decreased creatinine, inulin and p-aminohippurate clearances, but resulted in a significantly (P < 0.05) decreased fractional excretion of gentamicin (0.97 .+-. 0.24) (mean .+-. SD) compared to intact dogs (1.22 .+-. 0.08). Gentamicin serum protein binding by equilibrium dialysis was .apprx. 15% in both groups. In vitro canine cortical tissue slices accumulated drug as the slice/medium ratio was > 1 (1.77 .+-. 0.47). The renal handling of gentamicin is apparently altered in this disease model. This decreased fractional excretion of gentamicin implies that the quantity of drug excreted by the diseased kidney cannot be precisely predicted on the basis of glomerular filtration rate alone when drug dosage regimens are designed for patients with renal disease.